Search PubMed⌕ Search

Biomedical subjects

D R Morel

Publications and source records attributed to D R Morel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chronic angiotensin converting inhibition does not influence renal hemodynamic and function during cardiac surgery.

PURPOSE: Treatment with angiotensin-converting enzyme (ACE) inhibitors affects the autoregulation of renal blood flow and glomerular filtration and provides renal protective effects. The purpose of this case-control study was to investigate the effects of chronic ACE inhibition on perioperative renal hemodynamics and function. METHOD: We prospectively studied renal function in two groups of patients, chronically treated or not, with ACE inhibitors (ACEI and control; n = 16, in each group) who underwent elective cardiac surgery under hypothermic cardiopulmonary bypass. Glomerular filtration rate, effective renal plasma flow, osmolar clearance and fractional excretion of sodium and potassium were determined before, during and after CPB. Additional measurements included plasma atrial natriuretic factor (ANF) as well as plasma and urinary cyclic GMP (cGMP), thromboxane B2 (TxB2) and 6-keto-PGF1. RESULTS: Renal functional and hemodynamic variables did not differ between the two groups, at any period. Cardiopulmonary bypass induced increases in urinary flow, osmolar clearance and fractional excretion of sodium and potassium in both groups. Plasma and urinary ratio of 6-keto-PGF to TxB2 increased markedly and reflected a predominant systemic and renal release of vasodilatory prostaglandins. Intraoperatively, ANF was higher in ACEIs than in control patients. CONCLUSIONS: Long term treatment with ACE inhibitors does not influence the perioperative changes in renal hemodynamics and function. During cardiopulmonary bypass, a transient impairment in solute reabsorption is associated with renal release of vasodilatory mediators (nitric oxide and prostacyclin).

Aged↗
PubMed1999

Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans.

1. In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. 2. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. 3. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg(-1) in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 microg kg(-1) of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg(-1) in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 microg kg(-1), respectively. 4. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 microg kg(-1) in 200 microl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 microg kg(-1) of TASP-V when compared with saline. 5. It is concluded that intranasal or intrabronchial pretreatment with TASP-V reduced nasal obstruction and bronchoconstriction evoked by histamine challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine.

Adult↗
PubMed1999

Beneficial effects of leukocyte-depleted blood and low-potassium dextran solutions on microvascular permeability in preserved porcine lung.

Modified Euro-Collins (EC) solution, a crystalloid intracellular-type solution, has been commonly used for pulmonary preservation. Several experimental studies have shown the advantages of using extracellular colloid-based solutions. The aim of this study was to compare the quality of preservation of two extracellular colloid solutions, leukocyte-depleted blood (BL) and low-potassium dextran (LPD) solutions, with that of EC solution. Lungs of 22 domestic pigs were flushed and preserved with EC (n = 8), BL (n = 7), or LPD (n = 7) solution. After harvesting, one of the lungs was reperfused immediately in an ex vivo circuit (control lungs), whereas the contralateral lung was reperfused after 8 h of cold (4 degrees C) storage (preserved lungs). Besides the lung function parameters (gas exchange, pulmonary hemodynamics and mechanics), the permeability of the endothelial-epithelial barrier was assessed by determining the transferrin leak index (TLI) using a double radioisotopic method, by measuring the alveolar/arterial protein concentration ratio, and by analyzing histopathologic changes. The functional quality (oxygenation, airway resistance, dynamic compliance [CL, dyn]) of both BL and LPD lungs was slightly but significantly superior to that of EC lungs. However, pulmonary vascular resistance was lower in BL-preserved than in EC- or LPD-preserved lungs. The TLI was increased in EC control and preserved lungs, whereas it was low in BL and LPD control lungs and did not increase after preservation. The alveolar/arterial protein concentration ratio was not different between control groups, but was increased fourfold in EC-preserved compared with BL- or LPD-preserved lungs. Finally, EC-preserved lungs presented a weight gain about twice that of BL- and LPD-preserved lungs. Morphologic analysis confirmed these results, because in the EC-preserved lungs, rupture of alveolar septa and severe alveolar edema and hemorrhage were observed, whereas BL- and LPD-preserved lungs showed a relatively well-preserved structure. The results demonstrate that both BL and LPD flush solutions preserve the endothelial-epithelial barrier better than does EC solution. Although the quality of preservation is similar, pulmonary vascular resistance is higher in LPD-preserved than in BL-preserved lungs.

Animals↗
PubMed1998

Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia.

OBJECTIVE: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep. DESIGN: Randomised, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 12 adult instrumented, midazolam-sedated sheep. INTERVENTIONS: The animals were randomised to receive a 20-min continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10 microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25-30% increase in cardiac output by all three drugs during control conditions. MEASUREMENTS AND RESULTS: Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO2) and consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO2 and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO2 (especially in the coeliac trunk) observed during control conditions. CONCLUSIONS: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO2 and VO2.

Animals↗
PubMed1998

Role of nitric oxide in the regulation of regional blood flow and metabolism in anaesthetized pigs.

To investigate the contribution of nitric oxide in the regulation of regional blood flow and metabolism in vivo, we administered incremental doses of N omega-L-arginine-methyl ester (L-NAME 1, 3, 10, 30 and 100 mg kg-1, intravenously) in isoflurane anaesthetized pigs. The pulmonary vascular bed exhibited a greater sensitivity to the L-NAME-induced pressor effects compared with the systemic arterial bed as the slope of the dose-response curve was steeper (42.9 +/- 4.3 vs. 24.3 +/- 3.6, P < 0.05) and the dose of L-NAME required to induce a 25% pressure increase was lower (PD25 of 6.2 +/- 2.5 vs. 22.8 +/- 5.2 mg kg-1, P < 0.05). L-NAME infusion produced a dose-dependent reduction in cardiac output that was evenly distributed among the mesenteric, femoral, hepatic and carotid arterial circulation as demonstrated by unchanged regional blood flows-to-cardiac output ratios, except in the kidney where the L-NAME-induced vasoconstriction was most pronounced (renal blood flow/cardiac output decreased from 6.2 +/- 0.6 to 3.7 +/- 0.7% after 100 mg kg-1 of L-NAME, P < 0.05). After the administration of L-NAME 30 mg kg-1, intestinal O2 uptake (Vo2) increased (+39 +/- 3%, P < 0.05) whereas renal Vo2 tended to decrease (-19 +/- 4%, P = 0.07) and whole body Vo2 remained unchanged. Plasma noradrenaline and adrenaline concentrations did not change significantly with L-NAME infusion. These data demonstrate that in anaesthetized pigs, endogenous nitric oxide is most important for the regulation of pulmonary and renal blood flows and in spite of unchanged global metabolic demand, nitric oxide inhibition leads to an increase in intestinal Vo2 associated with enhanced gut motility without rise in circulating lactate levels.

Animals↗
PubMed1998

Benefits of intraoperative skin surface warming in cardiac surgical patients.

We have investigated patients undergoing cardiac surgery with hypothermic bypass to see if the addition of skin surface warming during systemic rewarming on bypass (heated group, n = 43) would improve perioperative thermal balance compared with conventional management without skin warming (control group, n = 43) in an open, randomized, controlled study. Intraoperative skin warming with a water mattress and forced warm air over the face, neck and shoulders attenuated the afterdrop in nasopharyngeal temperature after weaning from bypass (2.3 (1.2) degrees C and 1.3 (0.5) degrees C in the control and heated groups, respectively) (P < 0.05) and resulted in higher rectal temperature 4 h after surgery. Despite similar standard coagulation tests, heated patients had lower blood loss via the chest tubes (600 (264) ml vs 956 (448) ml in control patients) (P < 0.05) and less requirements for i.v. colloid infusion (1662 (404) ml vs 1994 (389) ml) (P < 0.05). There was a significant inverse correlation between rectal temperature on arrival in the ICU and postoperative blood loss (r = 0.57, P < 0.001). These data suggest that additional skin surface warming with a water mattress and forced warm air helped to preserve perioperative thermal balance and may contribute to reduced bleeding after cardiac surgery.

Adult↗
PubMed1998

Inhibitors of the renin angiotensin system: implications for the anaesthesiologist.

The major long-term benefits of angiotensin-converting enzyme (ACE) inhibitors have now clearly been demonstrated in patients with arterial hypertension, cardiac insufficiency, coronary artery disease and several renal diseases. Such long-term treatment markedly alters the cardiovascular response to anaesthesia and surgery, whereas preliminary data suggest that short-term renin angiotensin system blockade might provide perioperative organ protection and improved circulatory conditions. Besides the classic view that the conversion of angiotensin I to angiotensin II is mainly due to ACE, alternative pathways have recently been identified, including cathepsin G as well as chymostatin- and aprotinin-sensitive serine proteases that are released from mastocytes and endothelial cells and which are insensitive to the effects of ACE inhibitors. These proteases are thought to contribute to tissue perfusion under hypoxic conditions and to structural remodelling. In clinical practice, ACE inhibitors may be preferred to angiotensin II receptor antagonists since the former, besides reducing angiotensin II synthesis, also lead to an accumulation of kinins (e.g. bradykinin), which have important cardio- and renal protective effects through liberation of prostacyclin and nitric oxide in endothelial cells and through stimulation of guanylate cyclase to form cyclic GMP.

Journal Article↗
PubMed1998

Haemodynamic and metabolic changes induced by repeated episodes of hypoxia in pigs.

BACKGROUND: Repeated hypoxia and surgical trauma trigger a potent neuroendocrine response and their association is thought to play a pivotal role in the pathogenesis of multi-organ dysfunction. We investigated the cardiovascular and metabolic responses to repeated acute hypoxia in anaesthetised and surgically instrumented pigs. METHODS: Under ketamine-midazolam anaesthesia, 15 pigs were surgically instrumented for measurements of cardiac output, vascular pressures and organ blood flows. Lactate production and O2 uptake were determined in the brain, liver, kidney and intestine. Ten animals were subjected to two 12-min periods of ventilatory hypoxia (FIO2 = 7%) followed by re-oxygenation and 5 animals underwent 120-min normoxic ventilation (Control group). RESULTS: Both hypoxic challenges produced a comparable release of catecholamines that was associated with increased cardiac output and redistribution of blood flow away from the intestinal and renal areas towards the brain and the liver; O2 uptake was markedly reduced in the intestine (-56 +/- 10%, P < 0.05) and least affected in the brain and the kidney (-19 +/- 12% and -23 +/- 21%, respectively). During the second hypoxic test, lethal cardiovascular depression occurred in 5 animals; these non-survivors demonstrated impaired hyperdynamic response and incomplete recovery of intestinal O2 uptake during the first hypoxia/reoxygenation test. In the Control group, normoxic ventilation was not associated with significant haemodynamic and metabolic changes. CONCLUSION: Intraoperative hypoxia causes marked heterogeneity in organ blood flow and metabolism. The inability to develop a hyperdynamic cardiovascular response during a first hypoxic event, as well as a persistent intestinal O2 debt following re-oxygenation, predict the occurrence of death during the second hypoxic insult.

Anesthesia↗
PubMed1998

Effects of abdominal CO2 insufflation and changes of position on hepatic blood flow in anesthetized pigs.

During surgical laparoscopy, total hepatic blood flow (THBF) may be modified by CO2 insufflation, changes of tilt, ventilation with high tidal volume, hypercapnia, and anesthesia, but little information is available on the THBF during the procedure. To investigate the changes of hepatic blood flow following the combination of abdominal CO2 insufflation and changes of tilt, we measured mean arterial pressure (MAP), cardiac output, portal vein blood flow (PVBF), and hepatic artery blood flow (HABF) in anesthetized and ventilated pigs. CO2 was insufflated in the abdomen [intra-abdominal pressure (IAP) approximately 15 mmHg], and the hepatic blood flow was measured in various positions (horizontal, 10 degrees and 20 degrees head down, and 10 degrees and 20 degrees head up) before and during CO2 insufflation. CO2 insufflation in the horizontal position did not modify MAP, cardiac output, or PVBF but increased HABF. The head-up tilt decreased MAP, cardiac output, and both hepatic flows in the absence of pneumoperitoneum, but in the presence of abdominal CO2 only cardiac output and PVBF were decreased. The head-down tilt increased MAP and THBF in the absence of pneumoperitoneum, whereas no change was observed in the presence of abdominal CO2. The combination of CO2 insufflation and changes of tilt was not deleterious to hepatic perfusion. These results suggest that hepatic blood flow may be preserved during surgical laparoscopy if the tilt does not exceed 20 degrees and if IAP after CO2 insufflation remains <15 mmHg.

Abdomen↗
PubMed1998

The nitric oxide synthase/nitric oxide and heme oxygenase/carbon monoxide pathways in the human ureter.

OBJECTIVE: To investigate the nitric oxide synthase (NOS)/nitric oxide (NO) and heme oxygenase (HO)/carbon monoxide (CO) pathways in the human isolated ureter. METHODS: Immunohistochemical studies were performed. NOS activity was measured by monitoring the conversion of [3H]-arginine to [3H]-citrulline. Functional inhibitory effects mediated by NO and CO were assessed, and correlated with cyclic nucleotide levels. RESULTS: The overall innervation of the ureter was moderate, however more prominent in the distal segment. Relative to overall innervation, neuronal NOS-immunoreactive (-IR) nerves were few. In the submucosa, neuronal NOS-IR varicose nerves were found closely together with varicose nerves containing calcitonin gene-related peptide immunoreactivity. In the distal ureter, nerve trunks were demonstrated, expressing immunoreactivity for HO-2. Ca(2+)-dependent NOS activity was 53 +/- 13 pM/mg protein/h. In isolated preparations, NO decreased endothelin-1-induced contraction in a concentration-dependent manner. In strips exposed to NO, there was a 6-fold increase of the cyclic GMP levels in comparison to control preparations (p < 0.001). CO exerted no effect on induced ureteral tone. CONCLUSIONS: Neuronal NOS- and HO-2-IR nerves can be demonstrated in the human ureter, where NO, but probably not CO, may contribute to the regulation of tone. Although the physiological roles for NO and CO remain to be established, the NOS/NO/cyclic GMP pathway may be a target for drugs producing relaxation of the human ureter. The richer innervation of the distal ureter may be of importance for the coordination of ureteral peristalsis and the motility of the ureterovesical junction.

Adolescent↗
PubMed1998

Oxygen supply dependence of urea production in the isolated perfused rat liver.

To determine whether hepatic urea production is limited at low hepatic O2 delivery (DO2) by O2 itself or by the availability of substrate for urea synthesis, we isolated livers from normal rats and perfused them with Krebs-Henseleit bicarbonate (KHB) buffer, KHB + 5 mM NH4Cl, or KHB + 5 mM glutamine (Gln) as an NH3 donor. The pump flow was lowered in stages, and we determined at each flow rate inflow and outflow O2 content and urea levels in the outflow perfusate. Urea production in Gln-perfused livers remained constant at high DO2 and declined in direct proportion to DO2 below a critical oxygen delivery (DO2crit, the point below which the hepatic O2 consumption [VO2] becomes limited by the hepatic DO2). The DO2crit calculated from the urea release-DO2 relationship (147 +/- 32 microl/min/dry g) was similar to the DO2crit calculated from the VO2-DO2 relationship (158 +/- 26 microl/min/dry g). When Gln concentration and flow rate were maintained constant while decreasing PO2 in the inflow perfusate (as well as hepatic DO2), urea production declined below the DO2crit. Furthermore, when Gln concentration in the perfusate was gradually reduced while keeping hepatic DO2 constant, urea production decreased proportionally with Gln concentrations in the perfusate. Consequently, urea production is dependent on Gln and O2 availability and becomes limited at the same DO2crit determined by the VO2-DO2 relationship.

Ammonium Chloride↗
PubMed1997

TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria.

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.

Acute Disease↗
PubMed1997

Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells.

Little is known on the haemostatic profiles of human microvascular endothelial cells (MVEC) from different tissues. In addition it is not known whether MVEC from patients display the same haemostatic pattern as MVEC coming from healthy controls. To address these questions MVEC from human lung and brain were isolated and stimulated with tumour necrosis factor alpha (TNF) and E. coli lipopolysaccharide (LPS) for 24 h. The level and the kinetics of procoagulant activity (PCA) and thrombomodulin (TM) expression were found to be different depending on the tissue of origin and on the agonist used. In particular, the inducible PCA was higher in lung than in brain MVEC, an observation that may be related to the frequency of lung involvement in septic shock. Differences were also observed for tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) with MVEC supernatants or cell lysates. These variables were then measured in lung MVEC purified from patients with acute respiratory distress syndrome (ARDS) and compared to controls. Cells from ARDS patients constitutively expressed more PCA and PAI-1 than controls. The fibrinolytic potential, expressed as t-PA/PAI-1 ratio, was lower in ARDS than in lung MVEC. It is concluded that MVEC display different haemostatic features depending on the tissue they come from and that lung MVEC from ARDS patients present a procoagulant profile when compared with those from controls.

Adult↗
PubMed1996

Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery.

We studied 22 patients undergoing aortic surgery, allocated randomly to receive, before induction of anaesthesia, a single i.v. dose of enalapril 50 micrograms kg-1 or saline. During infrarenal aortic cross-clamping, we observed similar reductions in oxygen uptake in the two groups, despite greater systemic oxygen delivery in enalapril-treated patients; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration. Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow (r = 0.83 (saline group) and r = 0.65 (enalapril group)). Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group. We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery, renal plasma flow and glomerular filtration during aortic abdominal surgery.

Aged↗